Pharmaceutical composition and method for treating cachexia in humans due to cancer

ABSTRACT

A pharmaceutical composition and method of treatment is provided for retarding and/or reducing cachexia in humans due to carcinoma, sarcoma, and leukemia which comprises the administration of a therapeutically effective amount of a composition comprising friedelan-3-one contained in a physiologically acceptable solution sufficient to retard and/or reduce said cachexia.

This application is a continuation of application Ser. No. 580,270, filed Feb. 15, 1984, now abandoned, which is a divisional of Ser. No. 380,883, filed May 21, 1982, which is a continuation-in-part of copending application Ser. No. 195,080, filed Oct. 8, 1980, now abandoned, which is a continuation of application Ser. No. 064,587, filed Aug. 7, 1979, now abandoned, which is a continuation of application Ser. No. 852,960, filed Nov. 18, 1977, now abandoned, which is a continuation of application Ser. No. 700,150, filed June 28, 1976, now abandoned, which is a continuation-in-part of application Ser. No. 521,410, filed Nov. 6, 1974, now abandoned. The disclosures of these applications are incorporated herein by reference.

This invention relates to a pharmaceutical composition for the treatment of cachexia caused by various forms of cancer and to a method of treatment for retarding and/or reducing cachexia due to cancer in humans.

BACKGROUND OF THE INVENTION

Cancer is generally defined as an abnormal and unrestrained new growth in cells and tissues that produces adverse effects in man and which is often fatal. Thus, when for no understandable reason, cells and tissues grow more rapidly than normal and develop abnormal shapes and sizes and cease functioning in a normal manner, they are said to be malignant or cancerous.

Cancers can be divided into three broad groups: carcinomas, sarcomas, and leukemias or lymphomas. Carcinomas arise in the epithelia, the sheets of cells covering the surface of the body and the lining of various glands. Sarcomas generally arise in the supporting tissues, such as fibrous tissues and blood vessels; and leukemias or lymphomas arise in the blood-forming cells of the bone marrow and the lymph nodes. Carcinomas are the most prevalent, while sarcomas and leukemias are less so. These cancers can be further classified by the organs in which they originate or by the types of cell involved. Considered in this way, there are 100 or so distinct varieties of the disease. Roughly half of all cancer deaths are caused by cancer of three organs: the lung, the large intestine, and the breast.

Cancer in general has recognizable symptoms. Cancer can be debilitating and may be accompanied by loss of appetite, loss of weight, loss of strength, changes in disposition, and changes in skin tone. The symptoms are typical of cancerous cachexia.

Cachexia is defined as general physical wasting and malnutrition caused by chronic diseases, such as cancer or other debilitating diseases.

While it is appreciated that the field of cancer therapy has been the subject of intensive research and study in recent years in which a large phase of the study has been directed to chemotherapy, very few effective substances have been found for alleviating the condition of cachexia.

A pharmaceutical composition has now been discovered which is effective for retarding and/or reducing cachexia in humans due to carcinoma, sarcoma, and leukemia.

STATE OF THE ART

Tests on friedelan-3-one (also known as friedoolean-3-one) are reported together with other drugs in Cancer Research Supplement, Vol. 25, No. 5, June, 1965, in a paper entitled "Cancer Chemotherapy Screening Data XXXVII", pp. 1077 et seq., in particular page 1125. The compound was tested dissolved in carboxymethylcellulose and was administered into mice by injection (intraperitoneal). According to the paper, the data were reported only on compounds which did not demonstrate sufficient activity in cancer systems tested to warrant further investigation. Nevertheless, the same compound was found, in accordance with the present invention, to be beneficially active in the treatment of cachexia when administered orally in a physiologically acceptable solution to humans in therapeutically effective amounts.

OBJECTS OF THE INVENTION

It is thus an object of the invention to provide a pharmaceutical composition for use in the treatment of cachexia in humans due to carcinoma, sarcoma, and leukemia.

Another object of the invention is to provide a method for aiding in retarding or reducing cachexia in humans due to carcinoma, sarcoma, and leukemia by the administration of the pharmaceutical composition contained in a physiologically acceptable solution.

These and other objects of the invention will more clearly appear when taken in conjunction with the following disclosure and the accompanying claims.

STATEMENT OF THE INVENTION

Stating it broadly, the invention resides in a pharmaceutical composition for treating cancerous cachexia in humans comprising a small but therapeutically effective amount of friedelan-3-one dissolved in a pharmaceutically acceptable solution. (The compound "friedelan-3-one" is also known in the literature as "friedooleanan-3-one".) When the term "friedelan-3-one" is used, it also is meant to include the derivatives thereof having similar properties.

Preferably, the solution comprises dissolving the small but effective amount of friedelan-3-one in ethanol in amounts ranging from about 0.01% to 0.4% by weight of solution. This solution is used as a master solution from which doses are produced by adding a predetermined amount of said solution to a sufficient amount of a pharmaceutically or physiologically acceptable carrier, such as water or other beverage, to enable the oral consumption of the diluted composition by a patient under treatment. The term "beverage" herein is meant to include water, fruit juices, or other orally consumable liquid.

The dosage amounts may range preferably from about one to about fifteen drops (or even up to about 50 drops) of the aforementioned solution added to a beverage (e.g., water) to be taken by a patient at least before each meal on a daily basis under the supervision of a physician. The preferred master composition is one containing approximately 0.04% friedelan-3-one dissolved in ethanol. At this concentration, the master solution contains about 6.5 micrograms (μg) of the active ingredient per drop. The size of the foregoing drops using a No. 20 dropper is such that approximately 50 drops equals one milliliter (ml) of solution.

The foregoing drug may further contain pharmaceutical adjuvants, for example, chlorophyll and a phenolic resin, e.g., phenolformaldehyde. Thus, the pharmaceutical composition may comprise by weight about 0.01% to 0.4% of friedelan-3-one, about 0.006% to 0.12% chlorophyll, and about 0.6% to 3.7% of said phenolic resin dissolved in ethanol, a specific composition containing about 0.04% friedelan-3-one, about 0.2% chlorophyll, and 1.65% phenolic resin. The latter composition is obtained by dissolving 0.033 gr friedelan-3-one, 0.166 gr chlorophyll, and 1.3326 gr phenolic resin in 100 ml of ethanol. It appears that the adjuvants aid in counteracting odors typical of certain cancers.

While the doses suggested are very dilute, a slight side effect may occur when the foregoing composition is orally administered to a patient. Such side effects may be accompanied by a gradual rise in temperature accompanied by a slight headache and mild pains in certain joints and are not serious. Such headaches and/or pains can be treated with aspirin or other wellknown pain-relieving drugs.

A 0.04% solution of friedelan-3-one is obtained by dissolving about 0.033 gr of the compound in ethanol which has a density of about 0.79 grs/ml, 100 ml of ethanol weighing about 79 grams. About 6 to 7 micrograms (μg) of friedelan-3-one is contained in a drop of a 0.04% solution. While ethanol is preferred as the carrier, other pharmaceutically acceptable solvents for oral consumption by a patient may be employed.

The composition of the invention is used under a physician's direction in prescribed dosage amounts which may preferably vary from about 1 to 15 drops (or up to 50 drops), with each dose containing an amount of friedelan-3-one ranging from about 2 to 60 μg, and generally from about 6 to 15 μg.

As a general guideline, one drop of master solution per 10 kg of body weight is an acceptable dosage amount.

Observations of patients by a physician have indicated that the drug is not considered toxic when taken orally in dosage amounts of several or more drops of a 0.04% ethanol solution diluted in one, two, or more ounces of water or other beverage, e.g., fruit juices.

Dosage amounts of up to 5 or more drops of a 0.04% ethanol solution (based on 1 drop per 10 kilos of weight 4 times a day) diluted in a beverage taken several times a day over a period of time of several or more months have indicated the drug to be therapeutically effective in the treatment of cachexia in patients having Lymphocytic Lymphoma Diffuse, Hodgkin Lymphoma, and Cancer of the Cervix as characterized by improvement in appetite, sleep, retardation in weight loss, weight stabilization, etc.

Therapeutic activity of the composition of the invention in alleviating the effects of cachexia was also indicated in the treatment of other patients suffering from various forms of leukemia, lymphosarcoma, uterine cancer, etc.

An ethanol solution containing 0.04% by weight of friedelan-3-one was employed, one drop of solution (about 6 to 7 μg of friedelan-3-one) being used for each 10 kg of body weight taken 3 to 7 times a day, depending on the gravity of the illness. This corresponds to a daily dose rate per 10 kg of body weight of approximately 20 to 46 μg. The patients were treated from 2 to 22 months. In a number of cases, other methods of conventional therapy were used in conjunction with the pharmaceutical composition of the invention.

Of some twenty patients studied, fourteen responded beneficially to the treatment. Four exhibited regular results, while in two instances, there was no noticeable therapeutic effect. No serious side effects were observed. In many instances, the patient felt better even in the absence of the reduction of cancerous growth.

As will be apparent from the foregoing studies, the composition of the invention is beneficial in the treatment of cachexia of cancer-bearing humans by use of small but effective doses. As stated earlier, tests to date have not indicated any substantial degree of harmful toxicity with said composition.

Thus, by working over the composition ranges set forth hereinbefore, dosage amounts can be prescribed compatible with the system of the cancer-bearing patient. The small but effective dosage amounts when prescribed for a patient may range from a drop of the master solution to upwards of about 15 drops or more added to an orally consumable amount of beverage, the amount of drug being determined by an attending physician familiar with the case. It is preferred that, in diluting the ethanol composition in water for oral use, the final ethanol content of the solution not exceed 5% by weight and preferably below 2% or below 1%. Generally, the younger the patient, the lower the dosage amount over the range stated hereinabove, the preferred 1 to 15 drops of the master solution in water being administered orally at least once a day, and preferably at least once before each meal on a daily basis, until a determination has been made that the cachexia in the patient has been retarded and even reduced.

Although the present invention has been described in conjunction with preferred embodiments, it is to be understood that modifications and variations thereto may be resorted to without departing from the spirit and scope of the invention as those skilled in the art will readily understand. Such modifications and variations are considered to be within the purview and scope of the invention and the appended claims. 

What is claimed is:
 1. An orally-consumable pharmaceutical composition for use in retarding and/or reducing cachexia in humans consisting essentially of an ethanol solution with about 0.01% to 0.4% by weight of friedelan-3-one, said composition being administered orally at regular intervals on a daily basis by diluting a predetermined therapeutically effective amount thereof in a beverage sufficient to enable the oral ingestion of said solution, the amount of said friedelan-3-one being therapeutically sufficient to retard and/or reduce said cachexia.
 2. The pharmaceutical composition of claim 1, wherein said ethanol solution consists essentially of approximately 0.04% by weight of said friedelan-3-one. 